WO2016003080A1

WO2016003080A1 - Real-time inhalation toxicity testing device using lung model

Info

Publication number: WO2016003080A1
Application number: PCT/KR2015/005616
Authority: WO
Inventors: 이규홍; 양효선
Original assignee: 한국화학연구원
Priority date: 2014-07-01
Filing date: 2015-06-04
Publication date: 2016-01-07
Also published as: KR101603634B1; KR20160003948A

Abstract

The present invention relates to a real-time inhalation toxicity testing device using a lung model, and specifically provides a real-time inhalation toxicity testing device using a lung model, the testing device being provided with a lung model device having a similar structure to and performing similar functions as a human lung by having lung cells attached thereto, and the testing device detecting, in real-time, changes in electric signals being generated from the lung model device according to the damaged state of the lung cells due to inhalation of nanoparticles, thereby enabling inhalation toxicity testing on nanoparticles to be performed in an indirect way by determining changes in the state of the lung cells without using real laboratory animals, and especially, enabling the changes in the state of the lung cells to be determined in real-time.

Description

Real-time Inhalation Toxicity Test Device Using Lung Model

The present invention relates to a real-time inhalation toxicity test device using the lung model. More specifically, the lung model device is configured to attach lung cells to perform a structure and function similar to that of the human lung, and to change the electrical signal generated from the lung model device according to the damage state of lung cells by inhalation of nanoparticles. By detecting in real time, inhalation toxicity tests on nanoparticles can be carried out in an indirect manner that detects changes in the state of lung cells without the use of a real experimental animal. It relates to a real-time inhalation toxicity test device using the lung model.

If the 20th century was a micro era, the 21st century could be called the nano era. Nanotechnology can be classified into nanomaterials, nanodevices, and environmental and biotechnology-based technologies according to their applications.

These nanotechnologies artificially manipulate microscopic materials at the atomic or molecular level to create materials or devices with new properties and functions, which are the basis for information technology (IT) and other biotechnology (BT) technologies today. It is hailed as a cutting-edge technology for realizing).

However, while nanotechnology offers many benefits and benefits that can be recognized as a new technological revolution throughout the industry, it is also well known that there are potential risks. This is due to the nature of nanotechnology.

In other words, the smaller the particles, the larger the specific surface area ratio, and the smaller the larger the specific surface area ratio, the greater the toxicity when reacting with biological tissues. For example, some nanoparticles such as titanium dioxide, carbon powder, diesel particles, etc. It has already been found in academic experiments that the smaller the size, the stronger the toxicity. In addition, ultra-fine nanoparticles can be lodged deep into the alveoli or migrate to the brain without being trapped by the airways or mucous membranes. Furthermore, recent studies have reported that the accumulation of nanoparticles in the body causes diseases or central nervous system disorders. .

Therefore, in recent years, with the development of nanotechnology, the stability evaluation of nanotechnology has been actively progressed. For example, nanoparticle inhalation toxicity test that evaluates the toxicity generated when nanoparticles are inhaled and accumulated in the human body has been conducted in various experimental animals. Is being studied. Human hazard data obtained through the nanoparticle inhalation toxicity test is used as various basic data on nanoparticles throughout the industry such as nanofibers, cosmetics, semiconductors, and drug carriers.

In recent years, as the importance of such nanotechnology is highlighted, various types of tests such as evaluation of efficacy, safety, and environmental impact of nanoparticles on human body as well as tests on inhalation toxicity of nanoparticles are being performed. They all proceed in much the same way as inhalation toxicity tests in that they assess the effects of nanoparticles on the human body, and therefore, various tests on such nanoparticles are referred to collectively as inhalation toxicity tests.

In addition, the nanoparticles are present in the aerosol state, and the test for the nanoparticles can be equally applied to the particles having a particle size of the submicron zone that exists in the aerosol state, so the nanoparticles will be described below. Use as a concept that includes.

Since these nanoparticles have a very fine size, they can be transported directly to deep lungs and attached to lung tissue during human breathing. Therefore, inhalation toxicity tests on nanoparticles generally generate nanoparticles in an aerosol state and supply them to an exposure chamber of a certain size. It is proceeding by measuring.

That is, the nanoparticles are exposed to the experimental animals to inhale deep into the lungs of the experimental animals, and as the nanoparticles are inhaled and attached to the deep lungs, the health change state of the experimental animals is measured.

Such inhalation toxicity tests should be performed using experimental animals. Recently, the ethical problem of animal experiments has emerged, and the regulations on test methods using experimental animals have been continuously expanded. In addition, the inhalation toxicity test apparatus using a test animal has a problem that it is not easy to provide such a test apparatus because of its large size, high installation and operating costs, and a complicated structure.

The present invention is invented to solve the problems of the prior art, an object of the present invention is to configure a lung model device to attach lung cells to perform a structure and function similar to the human lung, lung by inhalation of nanoparticles By detecting changes in electrical signals from lung model devices in real time according to the damage state of cells, inhalation toxicity tests on nanoparticles can be performed in an indirect manner to identify changes in lung cells without the use of real laboratory animals. In particular, it is to provide a real-time inhalation toxicity test apparatus that can grasp the change in the state of lung cells in real time.

Another object of the present invention is to arrange a plurality of mesh tissue panels in order to position the mesh tissue panel having a small lattice spacing sequentially along the inflow direction of the nanoparticles, so that the lung model device can achieve a structure similar to the actual lung structure Therefore, it is to provide a real-time inhalation toxicity test apparatus that can improve the accuracy of the inhalation toxicity test without using an experimental animal.

The present invention provides a case, a breathing operation unit for introducing nanoparticles together with air into the space inside the case in such a manner as to repeatedly perform the inflow and discharge operation of the air into the space inside the case, the grid shape of the conductive material A lung model device which is formed in a space inside the case and includes a mesh tissue panel to which each of the grid lines is attached human or animal lung cells; And a signal detection unit connected to the mesh tissue panel to detect an electrical signal generated through the mesh tissue panel in real time.

In this case, a plurality of mesh tissue panels are mounted in the case, and the plurality of mesh tissue panels are each formed to have a different sized grid spacing, and the grid spacing along the inflow direction of nanoparticles in the space inside the case. This smaller sized mesh tissue panel can be arranged to be positioned sequentially.

In addition, the real-time inhalation toxicity test apparatus, the data processing unit for determining the damage state of the lung cells by receiving the electrical signal detected by the signal detection unit; And an output unit configured to output a determination result of the data processing unit.

In addition, the data processor may determine the damage state of the lung cells by comparing the separate database data with the electrical signal applied from the signal detection unit.

In addition, the database material may be formed by database the damage state of the lung cells in accordance with the electrical signal generated through the mesh tissue panel.

In addition, the breathing operation unit is a particle supply module for generating nanoparticles to flow into the inner space of the case with air; And an air discharge module for discharging air from the inner space of the case, and the particle supply module and the air discharge module may be repeatedly operated alternately.

In addition, the air discharge module includes a buffer bag which is mounted in communication with the inner space of the case so that the air flowing into the inner space of the case through the particle supply module passes through the plurality of mesh tissue panels to be introduced therein; The buffer bag is formed of an elastic material so as to recover its shape, and the air introduced into the inner space of the case may be discharged from the inner space of the case by the elastic restoring force of the buffer bag.

In addition, the case is mounted to the main pipe in communication with the internal space so that the air flow into and out of the inner space, the main pipe is branched into the inlet pipe and the discharge pipe, the inlet pipe is air and into the case inner space The particle supply module may be connected to allow the nanoparticles to flow therein, and the discharge pipe may be formed to have an open end to allow air to be discharged from the space inside the case.

In addition, the mesh tissue panel may be formed by uniformly culturing human or animal lung cells in each grid line.

According to the present invention, a lung model device is configured to attach lung cells to perform a structure and function similar to that of a human lung, and the electrical signal changes generated from the lung model device according to the damage state of lung cells by inhalation of nanoparticles. By detecting in real time, inhalation toxicity tests on nanoparticles can be carried out in an indirect manner in which the state of lung cells is changed without using an actual experimental animal, and in particular, the state of lung cells can be identified in real time. It has an effect.

In addition, by placing a plurality of mesh tissue panels in order to position the mesh tissue panel having a small lattice spacing in the direction along the inflow flow direction of the nanoparticles, the lung model device can achieve a structure similar to the actual lung structure, accordingly There is an effect that can improve the accuracy of the inhalation toxicity test without the use of experimental animals.

1 and 2 is a conceptual diagram schematically showing the configuration of a real-time inhalation toxicity test apparatus using a lung model according to an embodiment of the present invention,

3 is a functional block diagram conceptually showing the configuration of a device for testing inhalation toxicity using a lung model according to an embodiment of the present invention;

4 is a view schematically showing an arrangement state of a mesh tissue panel according to an embodiment of the present invention;

5 is a cross-sectional view schematically showing the internal structure of the lung model device according to an embodiment of the present invention,

6 and 7 are diagrams schematically showing the operating state of the lung model device according to an embodiment of the present invention.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. First of all, in adding reference numerals to the components of each drawing, it should be noted that the same reference numerals are used as much as possible even if displayed on different drawings. In addition, in describing the present invention, when it is determined that the detailed description of the related well-known configuration or function may obscure the gist of the present invention, the detailed description thereof will be omitted.

1 and 2 is a conceptual diagram schematically showing the configuration of a real-time inhalation toxicity test apparatus using a lung model according to an embodiment of the present invention, Figure 3 is a real-time inhalation using a lung model according to an embodiment of the present invention Functional block diagram conceptually illustrating the configuration of a toxicology test apparatus.

Inhalation toxicity test apparatus according to an embodiment of the present invention can perform the inhalation toxicity test for nanoparticles without using a real experimental animal using a lung model device that operates in a structure similar to the lung structure of a human or animal As a device, a device capable of performing inhalation toxicity assessment in real time.

First, when looking at the structure and function of the human lung, the lungs are semi-conical as a whole, there is a pair of left and right, and occupies most of the thoracic cavity facing each other with the mediastinum in between. The right lung is divided into three upper and lower lobes, and the left lung is divided into two upper and lower lobes.

These lungs are responsible for the respiratory function, the left and right lungs are connected to the organs (氣管), respectively. The trachea is divided into left and right bronchus at the height of the fifth thoracic vertebrae and enters the lungs from each of the lung gates. Branched and thinned, eventually reaching a bag-shaped alveoli. In other words, the parenchyma of the lungs is a collection of countless vesicles called alveoli, and the capillary network surrounds these countless alveoli tightly, and gas exchange with red blood cells occurs through the alveoli.

During inhalation during human breathing, air enters the lungs from the airways through the trachea and into the bronchus, bronchioles, and alveoli. During this inhalation, nanoparticles in the air can be inhaled deep into the human lung. The trachea, bronchus, bronchioles, alveoli sequentially form finer tissues. In general, larger particles are attached to the trachea or bronchus to inhale deep into the lungs, but very fine particles such as nanoparticles are bronchioles. And up to the alveoli.

Inhalation toxicity tests on nanoparticles are performed by breathing the nanoparticles deep into the lungs of the test animal and checking for changes in health status.

The real-time inhalation toxicity test apparatus using the lung model according to an embodiment of the present invention is a lung model device 10 having a structure and function similar to the human lung, and the electrical signal generated through the lung model device 10 in real time It is configured to include a signal detection unit 20 to detect. At this time, the data processing unit 30 receives the electrical signal detected by the signal detection unit 20 and the data processing unit 30 for outputting the data processing result of the data processing unit 30 and the output unit 40 to be configured Can be.

The lung model apparatus 10 is configured to alternately repeat the inflow and outflow operations of the case 100 and the air into and out of the case 10 and the inner space of the case 100. And a respiratory actuating unit 200 for introducing nanoparticles together with a mesh formed of a conductive material lattice to be disposed in an inner space of the case 100 and to which human or animal lung cells are attached to each lattice line. It comprises a tissue panel 300.

According to this structure, the lung model device 10 may perform the respiratory function of the lungs through the respiratory actuating unit 200, and nanoparticles introduced into the case 100 by the respiratory actuating unit 200 may pass through or Since the mesh tissue panel 300 in the form of a mesh to which the lung cells C are attached to be disposed so as to be attached, the tissue has a structure and function similar to that of a human or animal lung.

In this case, one mesh tissue panel 300 may be mounted in the inner space of the case 100 as shown in FIG. 1. Alternatively, a plurality of mesh tissue panels 300 may be mounted in the inner space of the case 100 as shown in FIG. 2. have. The plurality of mesh tissue panels 300 are formed to have different grid spacings of different sizes, and the mesh tissue panels 300 having smaller grid spacing along the inflow direction of the nanoparticles in the space of the case 100 are formed. It is preferably arranged to be positioned sequentially.

According to this structure, since the lung model device 10 has a structure very similar to the lungs of a real human or animal, the accuracy of the inhalation toxicity test for nanoparticles can be further improved. Detailed description will be described later.

The signal detection unit 20 is connected to the mesh tissue panel 300 and configured to detect an electrical signal generated through the mesh tissue panel 300 in real time. In more detail, the mesh tissue panel 300 is formed to have a grid line 301 of a conductive material, for example, a metal such as copper, and each of the grid lines 301 is attached with lung cell (C) tissue. . The signal detection unit 20 is electrically connected to the mesh tissue panel 300 to detect an electrical signal change generated through the mesh tissue panel 300 in real time.

For example, the signal detection unit 20 may be configured to measure the impedance generated through the mesh tissue panel 300 in real time, and may determine the state change of the lung cells C through the change of the impedance value. have. That is, the lung cells (C) attached to the mesh tissue panel 300 is damaged by the nanoparticles flowing into the space inside the case 100 or the active state is changed, in this case the grid of the mesh tissue panel 300 Since the electrical resistance value generated in the line 301 is changed, it is possible to determine the change state of the lung cells (C) by measuring this.

At this time, since the signal detection unit 20 measures the electrical signal generated from the mesh tissue panel 300 in real time, the inhalation toxicity test apparatus according to an embodiment of the present invention in accordance with the supply of nanoparticles lung cells in real time The change state of (C) can be judged.

In addition, the inhalation toxicity test apparatus according to an embodiment of the present invention may further include a data processor 30 and an output unit 40, the data processor 30 is detected by the signal detection unit 20 It is configured to receive an electrical signal and process the data to determine a damaged state of lung cells. The output unit 40 may be configured to output the determination result of the data processing unit 30 in the form of a display device or a voice broadcast.

In this case, the data processor 30 may determine the damage state of the lung cells C by comparing the electric signal received from the signal detection unit 20 with the separate database data. The database material may be formed in a manner of database-forming the damage state of the lung cells C in advance according to the electric signal value generated through the mesh tissue panel 300.

That is, the electrical signal values generated according to the active state of the lung cells C attached to the mesh tissue panel 300, for example, the degree of death of the lung cells C, may be previously databased to form a separate database unit ( 50, and the data processing unit 30 compares the electric signal value measured and applied in real time from the signal detection unit 20 with the electric signal value stored in the database unit 50 as shown in FIG. 3. In addition, a real-time inhalation toxicity test may be performed by extracting the active state of the lung cells C corresponding to the electric signal value from the database unit 50 and outputting the same through the output unit 40.

2 and 3, when a plurality of mesh tissue panels 300 are provided, the signal detection unit 20 may detect an electrical signal for each mesh tissue panel 300 in real time. Since the damage state of the lung cells (C) attached to each mesh tissue panel 300 can be discriminated and determined, respectively, more various types of test results can be obtained for evaluating inhalation toxicity of nanoparticles. have.

Next, the configuration of the lung model apparatus 10 will be described in detail with reference to FIGS. 4 to 7.

4 is a view schematically showing an arrangement state of a mesh tissue panel according to an embodiment of the present invention, and FIG. 5 is a cross-sectional view schematically showing an internal structure of a lung model device according to an embodiment of the present invention. 6 and 7 are diagrams schematically showing the operating state of the lung model device according to an embodiment of the present invention.

The lung model device 10 for inhalation toxicity test according to an embodiment of the present invention enables the inhalation toxicity test for nanoparticles without an experimental animal by allowing the nanoparticles to be inhaled through a structure similar to that of the human lung. Device to be able to perform, as described above comprises a case 100, a breathing operation unit 200 and a mesh tissue panel 300.

The case 100 may be formed in a general box shape in which a receiving space is formed therein. Since the air flow by the breathing operation unit 200 is generated in the case 100, the inner space is formed to have a cylindrical shape so that the air flows smoothly, or as shown in FIGS. 1 and 2, the rectangular pillar. It can be changed in various ways, such as can be formed in the shape of a polygonal column.

The breathing operation unit 200 is configured to perform a breathing operation by alternately repeating the inflow and outflow operation of the air into the space inside the case 100, and through such a breathing operation, the air into the space inside the case 100. It is configured to introduce the nanoparticles with. The respiratory operation unit 200 is a particle supply module 210 for generating nanoparticles to flow into the inner space of the case 100 together with air, and an air exhaust module for discharging air from the inner space of the case 100 ( 220). The inhalation function of the breathing operation is performed by the particle supply module 210, and the exhalation function of the breathing operation is performed by the air exhaust module 220.

The mesh tissue panel 300 is formed in a mesh grid form of a conductive material and mounted in the space inside the case 100. Each of the grid lines 301 formed of the conductive material is attached to lung cells C of a human or animal. . One such mesh tissue panel 300 may be mounted in the inner space of the case 100, but a plurality of mesh tissue panels 300 may be mounted to have a structure similar to that of a human or animal lung.

The plurality of mesh tissue panels 300: 310, 320, 330, and 340 are formed to have different grid spacings d1, d2, d3, and d4, respectively, as shown in FIGS. 4 and 5, and breathe in the space inside the case 100. The mesh tissue panel 300 having a smaller lattice spacing is sequentially disposed along the inflow flow direction of the nanoparticles by the operation unit 200.

In more detail, the mesh tissue panel 300 is formed in a mesh lattice shape and lung cells C are attached to each lattice line 301, which is a human or animal lung cell C to each lattice line 301. ) May be formed by uniformly culturing. As such, the method of culturing and attaching the cells may be achieved through various known cell culture methods, and thus a detailed description thereof will be omitted.

A plurality of such mesh tissue panels 300 are mounted, and are formed to have different lattice spacings (d1, d2, d3, d4) of different sizes, and meshes having a smaller lattice spacing along the inflow direction of the nanoparticles are provided. The tissue panel 300 is arranged to be sequentially placed.

That is, air and nanoparticles are introduced into the inner space of the case 100 from the outside by the particle supply module 210 of the respiratory operation unit 200 as described above. As shown in FIG. 5, mesh tissue panels 300 having smaller grid spacing are sequentially disposed. For example, as illustrated in FIGS. 2 and 3, four

mesh tissue panels

310, 320, 330, and 340 may be arranged in a line along the inflow direction of the nanoparticles, and may be disposed at the most upstream of the inflow flow direction of the nanoparticles. The positioned mesh tissue panel 310 has a relatively large lattice spacing d1, and then a

mesh tissue panel

320, 330, 340 may be arranged in a row so that the lattice spacing sequentially decreases downstream as d2, d3, and d4.

According to such a structure, when air and nanoparticles are introduced into the space inside the case 100 by the respiratory operation unit 200, the air and nanoparticles are arranged in the order of lattice sizes of the plurality of mesh tissue panels 300: 310, 320, 330, 340. It shows the flow passing sequentially. At this time, since the mesh tissue panel 310 located at the most upstream has a relatively large lattice spacing d1, a relatively large amount of nanoparticles pass, but the

mesh tissue panels

320, 330, 340 located downstream have a lattice spacing ( Since d2, d3, and d4 become smaller, the amount of nanoparticles passing through the

mesh tissue panels

320, 330, and 340 decreases sequentially.

That is, the nanoparticles introduced into the space inside the case 100 by the respiratory operation unit 200 partially pass through the mesh tissue panels 300: 310, 320, 330, 340 in the course of passing through the plurality of mesh tissue panels 300: 310, 320, 330, 340. The nanoparticles are attached to each other to pass through a plurality of mesh tissue panels (300: 310, 320, 330, 340). In particular, since the lattice spacing of the plurality of mesh tissue panels 300: 310, 320, 330, 340 decreases sequentially, the passage amount of the nanoparticles is further reduced in the process of passing through the mesh tissue panels 300: 310, 320, 330, 340.

In addition, the relatively large nanoparticles are difficult to pass through the mesh tissue panel 300, so it is easy to attach to the mesh tissue panel 300 located upstream, but the relatively small nanoparticles are mesh tissue panel 300. It may be relatively easy to pass through to reach and attach to the mesh tissue panel 300 located downstream.

The arrangement structure of such a mesh tissue panel 300 is similar to the lung structure. As described above, air is inhaled into the trachea, bronchus, bronchioles and alveoli during inhalation during respiration, and the trachea, bronchus, bronchioles and alveoli sequentially form a finer tissue structure. Similarly, in the mesh tissue panel 300 according to the exemplary embodiment of the present invention, the mesh tissue panel 300 having a smaller grid spacing is disposed along the inflow flow direction of the nanoparticles.

According to such a structure, the lung model device according to an embodiment of the present invention may have a structure similar to the actual lung structure, and in this structure, the breathing operation may be performed through the respiratory operation unit 200, and thus, the actual lung structure. And in a form very similar in function. That is, the lung model device according to an embodiment of the present invention has a structure similar to the lung through a plurality of mesh tissue panel 300, and by performing the respiratory function of the lung through the breathing operation unit 200, It is shaped very similar to the structure and function of the lungs and can be used to perform a variety of tests.

In particular, since the lung tissue (C) is attached to the mesh tissue panel 300, the inhalation toxicity test for the nanoparticles is performed without experiment animals in a manner of grasping the state change of the lung cells (C) according to the inhalation of the nanoparticles. can do. Such a change in the state of the lung cells (C) can be grasped through the electrical signal measured in real time by the signal detection unit 20 as described above.

As described above, four mesh tissue panels 300 may be provided, for example, the grid line 301 of each mesh tissue panel 300 includes trachea, bronchus, bronchiole and alveolar cells sequentially. Can be cultured and attached, this mesh tissue panel 300 can represent organs, bronchus, bronchioles and alveolar tissue, respectively. When the mesh tissue panel 300 is mounted in the space inside the case 100, and air and nanoparticles are introduced into the space inside the case 100 through the respiratory operation unit 200, the nanoparticles attached to the suction surface are inhaled. The lung tissue of the mesh tissue panel 300 may be damaged, and the inhalation toxicity test for the nanoparticles may be performed by examining whether the lung tissue is damaged or active.

Meanwhile, in addition to the four tissues described above, the lung tissue includes a wide variety of tissues such as alveolar ducts and alveolar cysts. For example, the lung tissues may be classified into 23 detailed tissues. The number of mesh tissue panels 300 and the type of cell tissue may be variously changed according to a user's needs, such as being cultured and attached to the lattice lines 301.

Next, look at the configuration of the respiratory operation unit 200 for performing the respiratory function of the lung in more detail.

The respiratory operation unit 200 alternately repeats the inflow and outflow of air to the space inside the case 100, and generates a nanoparticle to supply the air together with the air to the space inside the case 100 to supply the particle 210. And an air exhaust module 220 for discharging air from the inner space of the case 100. At this time, the particle supply module 210 and the air discharge module 220 alternately operates repeatedly.

According to this structure, the nanoparticles are introduced into the inner space of the case 100 together with the air through the particle supply module 210, and after the air is introduced, the air is discharged through the air exhaust module 220. Nano particles may be discharged together with the air discharged through the air discharge module 220.

That is, the nanoparticles are introduced into the inner space of the case 100 together with air through the particle supply module 210, while passing through the plurality of mesh tissue panels 300 while being introduced, and in this process, some nanoparticles are tactical. As described above, each lung cell C attached to the plurality of mesh tissue panels 300 may be attached. As the nanoparticles are attached to the lung cells (C) of the mesh tissue panel 300 during the inflow of the nanoparticles as described above, the air is discharged through the air exhaust module 220 to the lung cells (C). The attached nanoparticles are not discharged and remain attached to the lung cells (C). Of course, some nanoparticles that are not attached to the lung cells (C) may be discharged to the outside with the air during the air discharge process.

Therefore, when the respiratory operation unit 200 is operated, since the nanoparticles repeatedly enter the inner space of the case 100 and adhere to the lung cells C of the mesh tissue panel 300, when the respiratory operation unit 200 operates, The amount of nanoparticles attached to the cells (C) increases, which may result in damage or death of the lung cells (C). Since the characteristic change of the lung cells C causes a change in the electrical resistance of the mesh tissue panel 300, the lungs may be measured by measuring the electrical signal of the mesh tissue panel 300 in real time through the signal detection unit 20. Inhalation toxicity assessment of nanoparticles on cells (C) can be performed in real time.

The particle supply module 210 includes a particle generator 211 that generates nanoparticles, and an inner space of the case 100 so that nanoparticles generated from the particle generator 211 flow into the inner space of the case 100 together with air. It may be configured to include an air inlet pump 212 for introducing air to the. In this case, as shown in FIG. 5, the nanoparticles generated from the particle generator 211 are introduced into a separate mixing chamber 213, mixed with air by the air inflow pump 212 in the mixing chamber 213, and the case. 100 may be introduced into the interior space.

The air discharge module 220 includes a buffer bag 221 mounted in communication with the inner space of the case 100, and the buffer bag 221 is inside the case 100 through the particle supply module 210. The air flowing into the space is arranged to be introduced after passing through the plurality of mesh tissue panels 300.

That is, the air is introduced from the upper layer into the inner space of the case 100 based on the direction shown in FIG. 6, and the air is buffered so that the introduced air passes through the plurality of mesh tissue panels 300 and then flows into the buffer bag 221. The bag 221 is mounted in communication with the lower end of the case 100.

Therefore, air and nanoparticles introduced into the space inside the case 100 by the particle supply module 210 must be introduced into the buffer bag 221 after passing through the mesh tissue panel 300, thereby introducing air and nanoparticles. The flow is stably maintained in a form that passes through all of the plurality of mesh tissue panels 300.

On the other hand, the buffer bag 221 is formed of an elastic material so that the shape can be restored, it may be formed in the form of a kind of rubber balloon. Therefore, when the operation of the particle supply module 210 is completed and the inflow of air is stopped, as shown in FIG. 7, the inner space of the buffer bag 221 and the case 100 is prevented by the elastic restoring force of the buffer bag 221. Air is exhausted to the outside.

The air discharge module 220 may be sufficiently configured in the form having a buffer bag 221 of such an elastic material, but, further, an air discharge pump (not shown) that discharges air from the space inside the case 100. It may be configured to include. In this case, the buffer bag 221 need not be formed of an elastic material, it will be sufficient to simply be formed of a flexible material capable of changing the volume.

In addition, the buffer bag 221 is in communication with the inner space of the case 100 is formed so that the volume change, in the process of introducing air and nanoparticles into the inner space of the case 100 by the particle supply module 210 It is possible to prevent the pressure rise of the inner space of the case 100, thereby performing a function of smoothly maintaining the inflow of air and nanoparticles by the particle supply module 210.

Meanwhile, the main pipe 410 is mounted in the case 100 to communicate with the internal space so that air can flow in and out of the internal space, and the main pipe 410 branches into the inflow pipe 411 and the discharge pipe 412. The inlet pipe 411 is connected to the particle supply module 210 to allow air and nanoparticles to flow into the space inside the case 100, and the discharge pipe 412 discharges air from the space inside the case 100. The end is formed in an open shape so that it can be.

At this time, the branched portion of the main pipe 410 is equipped with a flow path switching valve 420 for selectively opening the inlet pipe 411 and the discharge pipe 412 as shown in Figure 5, the flow path switching valve 420 is configured to operate in conjunction with the operating state of the particle supply module 210 and the air discharge module 220. That is, the flow path switching valve 420 operates to open the inlet pipe 411 while the particle supply module 210 operates, and to open the discharge pipe 412 while the air discharge module 220 operates. .

According to this structure, air and nanoparticles supplied from the particle supply module 210 are introduced into the inner space of the case 100 through the inflow pipe 411 and the main pipe 410 as shown in FIG. 6, and the case (100) After passing through a plurality of mesh tissue panel 300 in the internal space sequentially enters the buffer bag 221. During the inflow of air and nanoparticles, the nanoparticles are attached to the lung cells C of the mesh tissue panel 300. Thereafter, when the operation of the particle supply module 210 is completed, air is discharged from the inner space of the case 100 by the elastic restoring force of the buffer bag 221 as shown in FIG. 7. The path through which air is discharged is discharged through the main pipe 410 and the discharge pipe 412 from the space inside the case 100.

By repeatedly performing this process, the nanoparticles are continuously introduced into the space inside the case 100, and then the inhalation toxicity of the nanoparticles is examined by examining the characteristic change of the lung cells (C) attached to the mesh tissue panel 300. Tests may be performed.

The above description is merely illustrative of the technical idea of the present invention, and those skilled in the art to which the present invention pertains may make various modifications and changes without departing from the essential characteristics of the present invention. Therefore, the embodiments disclosed in the present invention are not intended to limit the technical idea of the present invention but to describe the present invention, and the scope of the technical idea of the present invention is not limited by these embodiments. The protection scope of the present invention should be interpreted by the following claims, and all technical ideas within the equivalent scope should be interpreted as being included in the scope of the present invention.

Claims

A case, a respiratory operation unit for introducing nanoparticles together with air into the space inside the case in such a manner as to repeatedly perform the inflow and discharge operations of the air into the space inside the case; A lung model device disposed in the inner space of the case and including a mesh tissue panel to which the lung cells of a human or animal are attached to each lattice line; And

A signal detection unit connected to the mesh tissue panel to detect an electrical signal generated through the mesh tissue panel in real time

Real-time inhalation toxicity test device using a lung model comprising a.
The method of claim 1,

The mesh tissue panel is mounted in a plurality of the case,

The plurality of mesh tissue panels are each formed to have a different size grid spacing, the mesh tissue panel having a smaller grid spacing along the inflow flow direction of the nanoparticles in the inner space of the case are arranged so as to be sequentially located Real-time inhalation toxicity test device using a lung model characterized in that.
The method of claim 2,

A data processor configured to receive an electrical signal detected by the signal detection unit and determine a damage state of lung cells; And

An output unit for outputting a determination result of the data processing unit

Real-time inhalation toxicity test device using the lung model, characterized in that it further comprises.
The method of claim 3, wherein

The data processor is a real-time inhalation toxicity test apparatus using the lung model, characterized in that to determine the damage state of the lung cells by comparing the separate database data with the electrical signal applied from the signal detection unit.
The method of claim 4, wherein

The database material is a real-time inhalation toxicity test apparatus using a lung model, characterized in that formed by the database of damage state of lung cells in accordance with the electrical signal generated through the mesh tissue panel.
The method according to any one of claims 2 to 5,

The breathing operation unit

A particle supply module generating nanoparticles and introducing the same into the inner space of the case together with air; And

An air exhaust module for exhausting air from the inner space of the case

To include, The particle supply module and the air discharge module is a real-time inhalation toxicity test device using a lung model, characterized in that the operation repeatedly repeated.
The method of claim 6,

The air exhaust module

A buffer bag mounted in communication with the inner space of the case so that air flowing into the inner space of the case through the particle supply module passes through the plurality of mesh tissue panels and is introduced therethrough.

Includes, the buffer bag is formed of an elastic material to restore the shape, the air introduced into the inner space of the case is discharged from the inner space of the case by the elastic restoring force of the buffer bag using a lung model, characterized in that Real time inhalation toxicity test device.
The method of claim 6,

The main pipe is mounted to the case in communication with the internal space to enable the flow of air to the internal space,

The main pipe is branched into an inlet pipe and a discharge pipe, and the inlet pipe is connected to the particle supply module to allow air and nanoparticles to flow into the space inside the case, and the discharge pipe has air from the space inside the case. Real-time inhalation toxicity test device using the lung model, characterized in that the end is formed in an open form to be discharged.
The method according to any one of claims 1 to 5,

The mesh tissue panel

A device for real-time inhalation toxicity test using a lung model, characterized in that formed in a manner that uniformly cultured lung cells of human or animal in each grid line.